Ulcerative colitis (UC) is a manifestation of inflammatory bowel disease (IBD), which can cause inflammation of the intestinal tract. Ankylosing spondylitis (AS) is an inflammatory disease of the sacroiliac joints. Many studies have found that some UC patients progress to AS. In this study, we conducted a literature search and meta-analysis to investigate the prevalence of AS among UC patients during follow-up.2 statistical methods.The studies related to the AS among patients with UC were obtained from PubMed, Web of Science, Embase, and Cochrane Library databases since its inception-December 2022. The literature was screened strictly according to inclusion and exclusion criteria. Forest plots were used to detect the overall incidence of AS in UC and to compare the risk ratios for the development of AS in the UC. The heterogeneity of studies was assessed using I1) 17 studies with 98704 UC patients were included. 2)700 UC patients developed AS during follow-up . Human leukocyte antigen B27 (HLA-B27) was reported in 3 studies. HLA-B27 positivity was significantly higher than the incidence of HLA-B27 negativity in AS patients . There was significantly increased risk of AS development in HLA-B27 positive IBD patients . 3)The definite follow-up time was reported in 12 studies (range: 0.3–40 years). After follow-up for ≥5 years, the incidence of AS among patients with UC was 1.75% (95% CI: 0.62–3.37%). Meanwhile, after follow-up for <5 years, the incidence of AS among patients with UC was 1.41% (95% CI: 0.65–2.37%) which was significant.Patients with UC are more likely to develop AS in the future. Furthermore, the IBD patients are at a higher risk of AS who have positive HLA-B27. The incidence of AS increased with longer follow-up time. Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD)—an inflammatory disease of the gastrointestinal tract. In short, UC is a chronic autoimmune-related inflammatory disease. The clinical manifestations of UC mainly involve abdominal pain, diarrhea, and hematochezia . It has Ankylosing spondylitis (AS) is a chronic autoimmune disease that usually affects the sacroiliac joints and spinal attachments. Clinically, AS is characterized by inflammatory pain and stiffness of the back . AS may Human leukocyte antigen B27 (HLA-B27) is a characteristic test indicator for AS. However, the specificity and sensitivity of AS patients with HLA-B27 has been reportedly to be low in the presence of IBD . FurtherThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was used to guidance the systematic meta-analysis .The literatures about the development of AS in UC patients were collected from four foreign databases, which included PubMed, The Cochrane Library, Web of Science, and Embase since its inception-December 2022. In addition to, we also collected the relevant articles from conference abstracts and references.“Ulcerative Colitis”, “Idiopathic Proctocolitis”, “Ankylosing Spondylitis”, “Bechterew’s Disease” and so on were used as subject terms to search the relevant literature. We used the following search strategy for the PubMed database  on the occurrence of AS during UC follow-up were included.① No follow-up study.② Reviews, case reports, animal and cell-based experiments, etc.).③ Repeatedly included literature, literature with incomplete data indicators or where complete information was not available.Two reviewers  independently screened the literature strictly according to the inclusion and exclusion criteria and extracted data by a standardized form. The literature was managed using NoteExpress software. Initially, after eliminating duplicates for inclusion, the primary screening was done by reading the title and abstract of the literature. And then full-text literature was analyzed in detail. If there was disagreement between the 2 reviewers in the literature screening or data extraction process, the decision was submitted to a 3rd reviewers (WJY).Case-control studies and cohort studies were evaluated for methodological quality using the Newcastle-Ottawa Scale (NOS) . Cross-sP ≥ 0.10 and I2 ≤ 50%, the data were homogeneous across studies and were analysed using a fixed effects model. If P< 0.10 and/or I2 > 50%, we need to find the source of heterogeneity, or in cases where the source of heterogeneity was unclear, a random-effects model was used [The frequency of AS development in UC during follow-up was detected by a fixed or random-effects model. Literature heterogeneity was analysed using Revman 5.3 software and the R Statistical Software meta package. If was used . BesidesRegistration number: CRD42023405366.Our study did not involve human or animal experiments, which simply integrated results from other articles. Therefore, the study did not need to obtain ethical approval.The databases search yielded 2033 relevant studies, and 17 studies were finally included for meta-analysis in strict accordance with the inclusion and exclusion criteria of this study . But the heterogeneity was at a high level (I2: 93%). Due to the relatively small number of articles, data could not be removed to eliminate heterogeneity, and the source of heterogeneity was unclear (12 studies mentioned the follow-up duration of UC (range: 0.3–40 years). The follow-up time duration was ≥ 5 years in 7 studies, while the follow-up time duration was < 5 years in 5 studies. UC patients whose follow-up period ≥ 5 years were more likely to develop AS than those with follow-up period < 5 years (1.75% vs 1.41%). The risk of AS development among UC patients was significantly higher in studies that had a longer follow–up period (P<0.000) . There was significantly increased risk of AS development in HLA-B27 positive IBD patients  , implying that HLA-B27 positivity is an important risk factor for the development of AS. On the other hand, the risk of AS development in UC patients with ≥5 years of follow-up was reported to be 1.75% (95% CI: 0.62–3.37%) and 1.41% (95% CI: 0.65–2.37%) in UC patients with <5 years of follow-up (P < 0.05), indicating that the risk of AS in UC patients may increase over time.To the best of our knowledge, several studies have demonstrated a link between intestinal and joint inflammation –35. MoreHLA-B27 serves as the strongest genetic risk for AS, with 80–90% positivity reported in AS patients . Ossum AThe follow-up duration is associated with the occurrence of AS in UC patients. The low prevalence of AS in the UC patients who were followed up may be attributed to the relatively short duration of follow-up. Our study results showed that, after follow-up for ≥5 years, the incidence of AS among patients with UC was 1.75% (95% CI: 0.62–3.37%). Meanwhile, at a follow-up for <5 years, the incidence of AS among patients with UC was 1.41% (95% CI: 0.65–2.37%) which was deemed significant. Moreover, a retrospective analyses conducted in Korea did not find the onset of AS during 3.2 years of follow-up among pediatric patients with UC . It can There are, of course, limitations to our study. First, almost all included studies were retrospective case reports of AS in patients with UC. Second, the search literature was restricted to studies published in the English language. Many studies from other languages were not included in this study. Third, the therapy adopted for UC patients and their effects on AS development was also not studied. Finally, data collected on the gender or age of UC patients who developed AS was inadequate, which may have affected the calculation of the risk of developing AS in UC patients .In patients with UC, the risk of developing AS is higher than in the general population. In addition, the HLA-B27 positive in IBD patients is a risk factor for AS which need follow-up. Finally, odds of developing AS in UC patients may increase over time.


Although therapeutic progresses have significantly improved Overall Survival (OS), a number of patients do not respond to HD–MTX-based chemotherapy (15–25%) or experience relapse (25–50%) after an initial response. The reasons underlying this poor response to therapy are unknown. Thus, there is an urgent need to develop improved predictive models for PCNSL. In this study, we investigated whether radiomics features can improve outcome prediction in patients with PCNSL. A total of 80 patients diagnosed with PCNSL were enrolled. A patient sub-group, with complete Magnetic Resonance Imaging (MRI) series, were selected for the stratification analysis. Following radiomics feature extraction and selection, different Machine Learning (ML) models were tested for OS and Progression-free Survival (PFS) prediction. To assess the stability of the selected features, images from 23 patients scanned at three different time points were used to compute the Interclass Correlation Coefficient (ICC) and to evaluate the reproducibility of each feature for both original and normalized images. Features extracted from Z-score normalized images were significantly more stable than those extracted from non-normalized images with an improvement of about 38% on average ( Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) (PCNSL) is a rare form of aggressive extranodal non-Hodgkin’s lymphoma limited to the CNS and, thus, potentially involving the brain, spinal cord, meninges, and eyes ,2. MagneRadiomics is a computational technique to extract high-dimensional quantitative features from medical images , which eHerein, we report a machine learning-based approach for predicting one-year OS and PFS in patients with PCNSL undergoing treatment with a high-dose methotrexate-based chemotherapy regimen. The proposed method relies on extracting robust and stable radiomics features from MRI scans. Such robustness and stability was assessed by comparing different intensity normalization methods on patient images acquired at different time points. To our knowledge, only a few studies have investigated the importance of image normalization in radiomics studies, despite it constituting an important challenge when using MRI data. In fact, the definition of a protocol is still missing ,35,36,37Clinical and MRI data from 80 patients with histological or cytological diagnosis of PCNSL, as well as absence of extra-CNS disease as per international guidelines , treatedto correct the non-homogeneous intensity of the magnetic field present in MR images, the module “N4ITK MRI bias correction” available in 3D Slicer  was usedfor each patient, all available MRI acquisitions were registered on the T1-gd image (sequence where segmentation was performed);skull stripping  was perfnormalization methods were applied for MRI intensities normalization  .All images were pre-processed according to the steps described below see , in ordeThree gray level intensity normalization methods were tested on the MR images: Z-score, WhiteStripe and Nyul.The Z-score method normalizes the image The WhiteStripe method  was deveThe method developed from Nyul et al. , also cahttps://github.com/jcreinhold/intensity-normalization (accessed on 19 February 2023).The code used for this implementation is available at https://pyradiomics.readthedocs.io/en/latest/features.html, (accessed on 19 February 2023) [The hyperintense tumor lesion on post-contrast T1-W images was manually segmented for each patient resulting in volume of interest (VOI). The same VOI was reported in the other sequences for each patient applying the linear transformation identified by the registration process. All segmentations were performed by R.L., a radiologist with 4 years of experience, at the time of the study. Radiomics features were extracted from the VOI using Pyradiomics 3.0.1 (ry 2023) : 19 Firsry 2023) . In totahttps://scikit-learn.org/stable/modules/generated/sklearn.preprocessing.MinMaxScaler.html, accessed on 19 February 2023). Only relevant features were selected in cross validation according to an ensemble of four selection methods: (i) SelectKBest for the chi-square test method; (ii) the Recursive Feature Elimination (RFE) using the Logistic Regression model; (iii) least absolute shrinkage and selection operator (Lasso), and (iv) Select From Model using RandomForestClassifier model. In detail, each method extracted https://scikit-learn.org/stable/modules/generated/sklearn.model_selection.RepeatedStratifiedKFold.html, accessed on 19 February 2023) (10 repetitions) was adopted to assess overfitting and to evaluate the stability of the results. The workflow of this study is described in Given as input a set of radiomics features extracted from processed MRIs (Group A), the goal was to train a machine learning model to predict the probability of survival of a patient with PCNSL. Since the prediction task had only two possible outcomes (survive/not survive after 1 year), the task was modeled as a binary classification problem. A first selection of the features was performed, using a high correlation filter to remove variables having large absolute correlation. To overcome the curse of dimensionality issues and reduce overfitting, the Min–Max Normalization method was applied to linearly transform radiomics features by using scikit-learn library  was calculated to evaluate the reproducibility of each feature for each normalization method. Formally, the ICC is a descriptive statistic that can be used when quantitative measurements are made on units organized into groups . It rangICCs were computed to assess the stability of first-order and textural features across the three acquisitions before and after normalization. The Kruskal–Wallis test and its post hoc were used to compare the obtained ICCs for T1-w and T2-w sequences, under the assumption that data were not normally distributed. The best normalization method was applied to images of groups A/A2 for subsequent Radiomics analysis.Patients were dichotomized, based on OS or PFS greater than, or lower than, 12 months, respectively. OS was defined as time from diagnosis until death due to any cause or date of last follow-up visit, and PFS was defined as time from diagnosis until progression, relapse, death or date of last follow-up visit .https://scikit-learn.org/stable/modules/generated/sklearn.metrics.f1_score.html, accessed on 19 February 2023) and Area Under ROC curve (AUC) . It is worth noticing that machine learning model validation is a crucial step, especially in the biomedical domain. We also compared the performance of the classifiers using both radiomics features alone as well as combined with clinical features. Age > 60, PS > 2, LDH > ULN, protein CSF > ULN and deep lesion were considered as clinical features, these being considered as available and validating PCNSL risk scores [Each of the selected ML algorithms was trained at classifying OS for patients in Group A. Classification performances were evaluated in terms of F1-score , classification results obtained from images normalized with Z-score are presented in this section  and F1 = 0.77 (0.73–0.83). For T2-W sequence, the best performances were obtained by the SVM classifier with F1 = 0.80 (0.77–0.86) and LR with F1 = 0.80 (0.75–0.86). For T1-W/T2-W, the performance improved and we obtained a median of F1-score equal to 0.83 (0.77–0.86) with RF classifier. The best results were obtained from normalized images, with a significant statistical difference from the results obtained using features extracted from non-normalized images.When introducing clinical features, the results did not significantly change. In this case, the best performances were obtained with T1-W (KN = 0.82 (0.73–0.86) and T1-W/T2-W (ETC = 0.80 (0.73–0.86)). Instead, The F1-score for predicting OS using only clinical features was 0.71 (0.66–0.79) with the SVM classifier.p < p = 0.38).Patients of Group A2 were considered to assess PFS classification task. The patients’ characteristics are summarized in The addition of clinical features for PFS did not improve performances and, considering only clinical features, the best result was LR = 0.67 (0.63–0.71). Compared to OS prediction, in this case also the best performance was obtained with normalized images for the sequence T2-W and T1-W/T2-W with a statistical difference with non-normalized images.p-value < p = 0.002).ROC curves of the best performances for PFS classification  also shoBeyond the classification scores, further analyses were conducted to better understand the role of the features in the classification process. The study was performed for each imaging modality, with and without intensity normalization. We considered the RF classifier, where the feature importance was computed as the mean and standard deviation of accumulation of the impurity decreased within each tree of the forest. In more detail, for each independent training in the cross-validation procedure, we ranked the features according to importance score and selected the top 15 (top-15). Then, for each feature, we calculated the frequency with which that feature was selected as top-15 and, from the resulting distribution, we selected the top 13 features for analysis. Simply put, we selected the top 13 features most often ranked as “most important" in each independent training of the cross-validation procedure.https://pyradiomics.readthedocs.io/en/1.1.1/features.html#radiomics-firstorder-label, accessed on 19 February 2023) . For T1-W and T2-W sequences , GLCM features  and GLRLM features  received the highest scores.For T1-W and T2-W sequences  in the OS classification, the most important contribution was given by shape features (Elongation and Sphericity) and first order features , that shows the relationship between the two largest principal components in the ROI shape, and its value, ranging from 0 (line-like object) to 1 (circle-like object).Here, To the best of our knowledge, this is the first study investigating the capability of radiomics features as outcome predictors in patients with newly diagnosed PCNSL, while also evaluating the impact of MR image normalization  on featup-value < p-value < p-value < Significant results were obtained for both OS and PFS prediction using all the selected classifiers with a statistically significant difference , the proposed method made a breakthrough in radiomics-based precision medicine for PCNSL patients.


To determine whether the inclusion of white blood cell (WBC) counts in the SYNTAX score (SS) or SS II models could improve the models’ performance for risk stratification in individuals with chronic renal insufficiency (CRI) following percutaneous coronary intervention (PCI).In total, 2,313 patients with CRI, who were subjected to PCI and had data available on in-hospital WBC (ih-WBC) counts, were recruited. Patients were divided into 3 groups as per their ih-WBC counts . The primary endpoints were all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints incorporated myocardial infarction, stroke, unplanned revascularization, and major adverse cardiovascular and cerebrovascular events (MACCEs).p < 0.001), ACM , unplanned revascularization , and MACCEs  among the three groups. Multivariable Cox regression analysis depicted that the risk of ACM and CM in the high WBC group was 2.577  and 3.850  times that in the low WBC group after adjusting for other confounding factors. A combination of ih-WBC counts with SS or SS II significantly improved the risk assessment and prediction of ACM and CM.During a median follow-up of 3 years, the high WBC group had the highest incidences of CM (2.4% vs. 2.1% vs. 6.7%; The ih-WBC counts was associated with the risk of occurrence of ACM, CM, unplanned revascularization, and MACCEs in individuals with CRI following PCI. It provides an incremental predictive value for the occurrence of ACM and CM when included in SS or SS II models. Studies2) for ≥3 months (The white blood cell (WBC) counts are a widely-used and easily available marker of inflammation in clinical practice. Its predictive value as a marker for mortality in individuals with acute coronary syndrome (ACS) is well-established . Recentl3 months , is high3 months . In this2.2.1.2 who underwent PCI between January 2014 and September 2017 in Cangzhou Central Hospital, Hebei Medical University, were retrospectively enrolled in the study. After excluding 155 patients for whom ih-WBC counts data were not available, 2,313 patients were included in this investigation. Patients were classified into three groups as per tertiles of ih-WBC counts as follows: low WBC group [WBC counts ≤6.18*109/L (n = 776)], medium WBC group [WBC counts >6.18*109/L but ≤8.14*109/L (n = 768)], and high WBC group [WBC counts >8.14*109/L (n = 769)] ] . The stuThe clinical and interventional data of the participants were collected from the electronic medical record (EMR) system. The CrCl values were calculated utilizing the simplified Modification of Diet in Renal Disease (MDRD) equation. The ih-WBC counts were defined as the first WBC counts value from the EMR system. Two of three trained cardiologists  calculated the SS  and SS I2.2.via clinic visits or telephone conversations. The primary endpoints included all-cause mortality (ACM) as well as cardiac mortality (CM). Deaths that could not be attributed to non-cardiac causes were considered CM. The secondary endpoints included myocardial infarction (MI), stroke, unplanned revascularization, and major adverse cardiovascular and cerebrovascular events (MACCEs), defined as a composite of ACM, MI, stroke, and unplanned revascularization. MI was defined following the consensus document on the fourth universal definition ] plots were used to test for proportional hazard assumption. All potential confounders  were incorporated in the multivariate analyses. By combining ih-WBC counts with SS or SS II values, we assessed the improvements in model performance, risk classification, and discrimination; this was done by comparing the AUC of the two nested models employing the nonparametric deLong approach and computing the net reclassification improvement (NRI) as well as the integrated discrimination improvement (IDI) indices. A two-sided value of p < 0.05 was statistically significant. SPSS 24.0  and R Software Version 3.6.0  conducted all the statistical analyses of this investigation.Continuous variables are reported as mean ± standard deviation (SD) or medians with interquartile ranges (IQR). Categorical variables are presented as frequencies and percentages. Continuous variables were compared utilizing one-way ANOVAs or Kruskal-Wallis tests, when necessary. Chi-square or the Fisher exact tests, on the other hand, carried out comparisons of categorical variables. Patients who were lost to follow-up were deemed at risk until they were censored at the date of the last contact. The cumulative event rates were measured utilizing Kaplan–Meier curves and compared across groups 3.3.1.9/L to 32.7*109/L. The SS values ranged from 1.0 to 47.0, and the SS-II values ranged from 9.7 to 59.6. Patients with high ih-WBC counts were younger and more likely to have current smoker status; clinical presentation of MI; reduced eGFR; lower left ventricular ejection fraction (LVEF); higher left ventricular end-diastolic diameter (LVEDD); and elevated levels of serum creatinine, blood glucose, total cholesterol, triglyceride, and low-density lipoprotein (p < 0.05 or p < 0.001) than those with low and median ih-WBC counts. Patients with high ih-WBC counts also had higher baseline SS values and were more likely to have thrombus lesions and undergo primary PCI   , 2.3.2.p < 0.001), CM , unplanned revascularization , and MACCEs  (p < 0.001) and 3.850  times that in the low WBC group after adjusting for other confounding factors (The median follow-up period was 3 years (IQR = 1.5–5.0). Among the three groups, the high ih-WBC counts group had the highest 5-year cumulative event rates of ACM  . Univari factors .3.3.p < 0.05) during the 30-month follow-up period. However, the degree of increase tended to decrease with time. There was no remarkable difference between the predictive value of the SS plus ih-WBC counts model and the SS model (p > 0.05) when the follow-up times were longer than 30 months. A similar result was observed for the SS-II models, albeit with a cutoff value of 28 months instead of 30 months. In the models used to predict the incidence of CM, though the extent of increase also tended to decrease with time, there was a remarkable difference between the predictive value of the SS plus ih-WBC counts model and the SS model (p < 0.05) during the whole follow-up period, and for the SS-II models, the cutoff value was 33 months  for ACM and 0.022 (p < 0.001) for CM and the IDI indices of the SS-II plus ih-WBC counts model over the SS-II model were 0.025 (p < 0.001) for ACM and 0.032 (p < 0.001) for CM Furthermore, by combining the ih-WBC counts with SS or SS II models, the metrics for risk reclassification and discrimination were significantly improved. The respective NRIs of the SS plus ih-WBC counts model over the SS model were 0.121 for ACM and 0.188 for CM; the NRIs of the SS-II plus ih-WBC counts model over the SS-II model were 0.025 for ACM and 0.135 for CM. The IDI indices of the SS plus ih-WBC counts model over the SS model were 0.019  . StudiesThe SS model is a well-established tool used to predict adverse clinical outcomes to help clinicians decide on optimum revascularization strategies in individuals with complex CAD , 24, 25.The SS-II model was created according to a Cox proportional hazards model utilizing the SYNTAX trial findings . The bas5.Despite these promising results, our results should be viewed in the light of multiple limitations. First, this study is based on data from a single center and is retrospective and observational in nature; therefore, it can only identify associations and cannot ascribe causality to related events. Second, differences in blood collection periods from the occurrence of the index event were not controlled for in this analysis. Third, we did not collect information on differential WBC counts and hs-CRP levels, both of which may be important for clinical outcomes. Finally, in some patients, we believe that the ih-WBC counts data may have been affected by undetected infections or other conditions for which we have no information.6.In patients with CRI following PCI, an elevated ih-WBC counts was found to be associated with the risk of occurrence of ACM, CM, unplanned revascularization, and MACCEs. A combination of ih-WBC counts with SS or SS II models significantly improved these models’ performance in predicting ACM and CM.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of Cangzhou Central Hospital, Hebei Medical University. The patients/participants provided their written informed consent to participate in this study.WY, LY, and ML provided the conception of the idea for the study and analyzed the acquired data. LY, WY, ML, SZ, and YL contributed to the development of the methodology and wrote the manuscript. FL, JW, NY, and MC were responsible for the interpretation of statistical results. XC revised the manuscript. All authors contributed to the article and approved the submitted version.This work was supported by the Natural Science Foundation of Hebei Province, China (H2021110008) and Hebei Provence Key Research Projects (172777163).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


After 30 days of contact lens wear, the subjects were re-evaluated to determine the changes in conjunctival redness, subjective dry eye disease, tear meniscus height, lipid pattern, and non-invasive break-up time. Results showed that the lipid layer thickness decreased significantly from 2.05 ± 1.53 to 0.92 ± 1.09 Guillon patterns, and the tear meniscus height decreased from 0.21 ± 0.04 to 0.14 ± 0.03. The mean pre-lens non-invasive break-up time (NIBUT) significantly increased from 15.19 ± 9.54 to 25.31 ± 15.81 s. The standard Patient Evaluation of Eye Disease (SPEED) score also decreased from 7.39 ± 4.39 to 5.53 ± 4.83. The results suggest that Lehfilcon A significantly reduced lipid and aqueous tear film volume but improved break-up time and subjective dry eye symptoms.This study aimed to evaluate the non-invasive and subjective symptoms associated with Lehfilcon A water gradient silicone hydrogel contact lenses with bacterial and lipid resistance technology. A prospective, longitudinal, single-centre, self-controlled study was conducted among silicone hydrogel contact lens wearers. Non-invasive analysis of the pre-lens tear film was performed using the Integrated Clinical Platform (ICP) Ocular Surface Analyzer (OSA), and the meibomian glands were evaluated with the Cobra The success of soft contact lenses (SCLs) is largely determined by compatibility and how well they work with the ocular environment. It is influenced by multiple factors that do not disrupt the stability of the ocular surface ,2. SilicSCL modifies the precorneal lacrimal dynamics and divides it into one pre-lens and one post-lens, each with less thickness than the initial physiological thickness . ConcurrSpecialised industries, including those in the field of contact lens manufacturing, are aimed at improving SCL properties that have the greatest impact on safety, comfort or tolerance of use, such as the module, contact angle, coefficient of friction and oxygen transmissibility ,13. HoweTear film stability assessment with non-invasive automated technology is a potentially effective methodology to evaluate the ocular environment differences created by SCL . The pro® biomimetic surface properties. These parameters included conjunctival redness classification, lipid layer thickness using an interferometer, tear meniscus height, the first and mean non-invasive break-up time (NIBUT), lid opening time, CLDEQ8, and SPEED. All these measurements were taken in order to gain a better understanding of the properties of these specific contact lenses and how they impact the eye.The purpose of the study was to evaluate various parameters in individuals who wear silicone hydrogel contact lenses with CelligentWe conducted this prospective, longitudinal, single-centre self-control study with a timeline of 30 days. It was performed at the Optics and Optometry cabinets of the Pharmacy School (University of Seville). This research was conducted according to the Helsinki Declaration and the Ethical Committee Board of the University of Seville (0384-N-22).All the subjects included in the final analysis read and signed the informed consent form. An informative sheet was provided to all subjects with the detailed study procedure. The inclusion criteria were as follows: (1) healthy subjects without any eye disease or eye treatment, (2) age between 18 and 35 years old, (3) Contact Lens Dry Eye Questionnaire 8 (CLDEQ8) score above 0 points , (4) dai® . The device was previously described in detail [® HD . The degree of meibomian gland dysfunction (MGD) was measured using the ImageJ method defined by Pult and Nichols [The non-invasive pre-lens tear film analysis was performed using the Integrated Clinical Platform (ICP) Ocular Surface Analyzer (OSA) from SBM Systemn detail . The mei Nichols . MGD was®  with a monthly replacement schedule and daily wear. It belongs to the Food and Drug Administration (FDA) material group and has a high-water content, is non-ionic (V-B), and has Biomimetic Celligent® Technology that provides resistance to bacteria and lipid deposits. The water gradient technology within the lens results in a high-water content (>90%) at the outermost surface.Two subjective dry eye disease questionnaires were used: the Contact Lens Dry Eye Questionnaire 8 (CLDEQ-8)  and the ® Care Hyaluropolimer Plus 360 mL, Servilens Fit and Cover® , for contact lens care. The solution contained 0.00015% polyhexamethylene biguanide (PHMB), 0.01% ethylenediaminetetraacetic acid (EDTA), sodium hyaluronate, and hydroxyethyl cellulose in an isotonic, buffered aqueous solution.All study subjects used the same multipurpose solution (MPS), Lens 55®).In the first phase, subjects were included or excluded according to previously defined criteria. The subject’s samples were obtained from the non-optometry academic community. Standard contact lens protocol adaptation was performed according to the Graeme Young Soft Lens Design and Fitting chapter in the Nathan Efron Contact Lens Practice Book. All subjects were instructed to abstain from using any contact lenses, lubricants, or drops for a week prior to the study. After this wash-out period, they underwent a non-invasive examination and filled out subjective questionnaires, as previously described, to evaluate minor to major tear film fluctuations. The variables assessed were conjunctival redness classification (CRC), lipid layer thickness (LLT), tear meniscus height (TMH), first non-invasive break-up time (FNIBUT), mean NIBUT, lid opening time (LOT), CLDEQ-8, SPEED, and the degree of Meibomian gland dysfunction (MGD) measured using an infrared non-contact camera. Meibography was performed using a digital fundus camera  for 30 days. The aim was to evaluate the volume, stability, and lipid pattern of the short-term tear film in front of the lenses. All measures were performed with the contact lenses on, and the subjects were instructed to use only the provided lens care regimen and avoid using eye drops or lubricants. The temperature and humidity conditions were stable during all measurements, and the ocular surface test was alternated between the eyes. The subjects were asked to blink normally within one minute between OSA measurement steps and intentionally blink three times before the next measurement.p value < 0.05). The sample size was estimated using the GRANMO® calculator . A two-tailed test was used. Alpha and beta risks are set at 5% and 20%, respectively. The estimated standard deviation (SD) of the difference was set to 0.45 . Descriptive analyses were performed using the mean ± SD . The normal distribution of the data was assessed using the Shapiro-Wilk test. Differences in qualitative variables were assessed using the chi-square test. Differences between previous, short-term, and one-month Pre-lens variables were performed using the Wilcoxon test. For all tests, the significance level was set at 95% , and thThirty-one silicone hydrogel contact fittings were performed in a sample of thirty-one myopic with low astigmatism subjects (random eye selected). Descriptive analyses of sex, nationality, age, non-cycloplegic manifest refraction, LogMAR and decimal visual acuity, corneal meridian, contact lens power, and superior and inferior eyelid meibomian gland dysfunction are presented in p = 0.14). A modest effect size of 0.22 was reported. Lipid layer thickness interferometry decreased 1.20 ± 1.39 grades on the Guillon Scale . A large effect size of 0.85 was reported. Lipid layer interferometry before and one month after CL is presented in p < 0.01). A large effect size of 1.97 was reported. TMH before and one month after CL is presented in p = 0.09). A 0.29 modest effect size was reported. MNIBUT achieved a statistically and clinically significant difference of 10.00 ± 15.93 s. . A large effect size of 0.77 was reported. Finally, LOT showed the largest increase of 20.03 ± 26.50 s. . A large effect size of 0.82 was reported. TMH, FNIBUT, MNIBUT and LOT longitudinal changes are presented in a box and plot graph in Conjunctival redness classification achieved a non-statistically significant increase of 0.13 ± 0.70 grades on the Efron Scale . A trivial size effect of 0.11 was reported. Finally, SPEED significantly decreased within 1.83 ± 6.24 score points . A modest size effect of 0.40 was reported. CLDEQ8 and SPEED longitudinal changes are presented in a box and plot graph in CLDEQ8 remained similar, with a slight decrease of 0.70 ± 9.24 score points , and there was simultaneously a greater atmospheric exposure to the desiccation of the anterior surface of the SH-SCL. Eftimov et al. [The LOT showed significant increases in opening times between blinks in subjects carrying Lehfilcon A compared to the baseline results , while MNIBUT increased by 10.12 s .In this work, we verified that the scores on the CLEDQ8 and SPEED tests decreased significantly after one month of CL wearing; therefore, the symptoms were less severe after one month of use. Both questionnaires were previously validated by other authors ,53, alth® HD, which is a novel and innovative approach to evaluating the effectiveness of contact lenses in managing dry eye disease. The results of the study demonstrate that Lehfilcon A contact lenses significantly reduce lipid and aqueous tear film volume, increase pre-lens non-invasive break-up time, and improve subjective dry eye symptoms.This research adds novelty to the field by evaluating the effectiveness of Lehfilcon A water gradient silicone hydrogel contact lenses with bacterial and lipid resistance technology in managing dry eye symptoms. This is a prospective, longitudinal, single-centre, self-controlled study, which is unique in its design and provides a more comprehensive understanding of the impact of these contact lenses on ocular surface health. The study uses non-invasive pre-lens tear film analysis with the Integrated Clinical Platform (ICP) Ocular Surface Analyzer (OSA) and Meibomian gland evaluation with the infrared meibographer CobraRegarding the limitations, first, this research failed to compare several water gradient materials or a control group with well-known CL material. Second, the design of the manuscript is based on a refit of contact lenses, which could introduce significant bias. Third, future studies should evaluate both with and without lenses at baseline and after the wearer period. Finally, inflammation biomarkers or cytology impression analysis were not included due to the unavailability of technology. Third, the sample size in the study is limited, with only a small number of participants being evaluated. The power calculation of our study was set at 80%. Future research should include the relationship between the ocular surface and the changes produced by an SH-SCL with objective, automated and non-invasive methods, as well as establish protocols that help to select the suitable CL for each case. In addition, future studies could divide subjects into the dry eye and non-dry-eye groups. Furthermore, a control group with other treatments should be added in future research.This study provides valuable insights into the impact of Lehfilcon A water gradient silicone hydrogel contact lenses with bacterial and lipid resistance technology in managing dry eye symptoms. The results demonstrate that these contact lenses have a positive effect on reducing lipid and aqueous tear film volume, increasing pre-lens non-invasive break-up time, and improving subjective dry eye symptoms.


Sixty-six nursing home residents and 139 community-dwelling elderly subjects participated. Marital status, medical history, medication including vitamin D supplements, smoking, past fractures were assessed. Weight and height were measured and body mass index calculated. Serum 25-hydroxyvitamin D (25-OHD), PTH, Ca, phosphate, creatinine and eGFR were determined.vs. 36.7 nmol/l, [26.9-50], p < 0.001), PTH was higher  and 25-OHD deficiency was more prevalent  as was elevated PTH . 25-OHD correlated negatively with PTH . Hip fractures were reported by 8% of the residents and 2% of the independent elderly. The only predictor for hip fracture was elevated PTH (OR = 7.6 (1.5-36.9), p = 0.013). : In the nursing home residents 25-OHD was lower (17.8 nmol/l, [9.4-28.6]  : The prevalence of vitamin D deficiency and secondary hyperparathyroidism was high in the institutionalized subjects. Hip fracture risk was associated with elevated PTH and not directly with vitamin D levels or the residency status. The term Vitamin D designates a group of steroid compounds that are essential for human health . The majThe aim of the study was to compare the prevalence of vitamin D deficiency and self-reported fracture history among nursing home residents and community-dwelling elderly subjects and explore the association of vitamin D levels with the gender, body mass index and the prevalence of secondary hyperparathyroidism (SHPT).The study was a part of a cross-sectional screening study of the prevalence of vitamin D deficiency and the most common endocrine disorders in the Bulgarian population, carried out in January and February 2012 in 12 towns and the adjacent rural areas. Details on the initial study cohort recruitment and characteristics and the general vitamin D state of the population are published elsewhere .2 of body surface area 41 and Scr is expressed in mg/d  was calculated by the standard formula. Fasting venous blood was sampled and serum was stored at -20 C for serum 25-OHD, PTH, Ca, inorganic phosphate (iP), creatinine, and TSH determination. eGFR was calculated by the CKD-EPI formula: GFR = 175 × standardized Scr−1.154 × age−0.203 × 1.212 [if black] × 0.742 [if female], where GFR is expressed as mL/min/1.73 mThe fractures were reported as any fractures and separately for the hip, Colles’ and vertebral fractures.3 was applied as an internal standard with reaction monitoring for the respective m/z transitions: 401→383 for 25D3, 413→395 for 25D2, and 404→386 for d325D3. The method complies with the FDA required selectivity, matrix effect, accuracy, precision within 7.5% and extraction recoveries averaging 57-73%. Linearity was within 3.0-300.0 nmol/L, R2 > 0.99 (25-OHD was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) utilizing extraction with hexane. d325D2 > 0.99 . Based o® DxC 660i System, Beckman Coulter, Access HYPER sensitive hTSH) with a reference range between 0.34-5.60 mIU/l. Serum calcium, inorganic phosphate, creatinine and alkaline phosphatase were measured by an automated analyzer.PTH was determined by chemiluminesce with an Immunoradiometric assay (IRMA) Access2/DxI, reference range 1.3-9.3 pmol/l. TSH was measured as a possible confounder and was determined by a two-site immunoenzymatic “sandwich” assay . All numerical data were presented as means and standard deviations or median and interquartile range. Normality of distribution was explored by Kolmogorov-Smirnov test. Student t-test was used to compare the difference between different categories of normally distributed continuous variables. Mann-Whitney U test and median test were applied for non-normally distributed variables. Proportions were expressed as percent and 95% confidence intervals and compared by Chi-square and Fisher’s exact test. A logistic regression was performed to explore the effect of multiple factors on the prevalence of vitamin D deficiency. Spearman’s rho was used to measure correlations between the studied continuous variables. All correlations of 25(OH)D were performed after controlling for age and gender. All tests were two-sided, with a level of significance at p < 0.05.versus 9.1% [2.2-16] of the nursing home residents.Eight of the community-dwelling subjects and none of the nursing home residents reported vitamin D supplement use. The reported average daily intake was between less than 100 and 400 IU. The 25-OHD levels of the supplement-users did not differ from the group mean value and therefore were not excluded from the analysis. Of the community-dwelling subjects, 69.8% [62.2-77.4] lived with a spouse The nursing home residents were significantly older than the community-dwelling subjects and all further analyses were adjusted for age. The two groups differed in the female-to-male ratio  and wereThe comparison of the major group characteristics between the community-dwelling elderly and the nursing home residents is presented in Tables 1 and 2.We calculated eGFR in order to rule out a possible effect of chronic kidney disease. eGFR of the subjects did not differ between the two groups and correlated negatively with the age , but not with the PTH levels . It correlated negatively with 25-OHD in the institutionalized subjects . The oddvs. 33.4 ± 1.3, p = 0.064), but not in those with any fracture or with Colles’ fractures.The prevalence of any fractures or Colles’ fractures did not differ between the two groups . Only fovs. 3%, p = 0.048) but the count was too small for definite conclusions. There was no difference in the all fracture and Colles’ fracture prevalence among the subjects with normal or elevated PTH. In a logistic regression model adjusted for age, gender, 25-OHD level, eGFR, TSH, resident/not-resident the only factor significantly affecting the risk of a hip fracture was the elevated PTH with an OR = 7.6 (1.5-36.9), p = 0.013.In both groups the 25-OHD levels correlated negatively with PTH, but with none of the other variables . SHPT, evs. 75%. Severe vitamin D deficiency was found in every third resident. Our results do not differ from those reported by other authors from various geographic regions. Maeda and cols. for instance measured similar winter levels and difference between community-dwelling elderly and nursing home residents (In our winter study we compared community-dwelling elderly and institutionalized subjects and observed significantly lower vitamin D levels and higher prevalence of vitamin D deficiency in the latter – 95% esidents . Their sesidents .Various factors contribute to the low vitamin D state in the institutionalized elderly. Similar to our data, a Romanian team reported recently that none of the nursing home residents whom they studied received vitamin D supplementation . The vitThe sun exposure therefore might be the major factor that differentiates the two studied groups. There are few data in the literature researching the topic of sun exposure and vitamin D in nursing home residents. Nashimoto and cols. reported a distinct association between 25-hydroxyvitamin D levels and hours of sun exposure in institutionalized elderly . A pivotThe hip fracture rate in the institutionalized elderly and in those with severe vitamin D deficiency was marginally higher than among the independent elderly or those with higher 25-hydroxyvitamin D levels. Similarly to the results of other authors, 25-hydroxyvitamin D was lower in the subjects reporting hip fractures . On the We observed no association of vitamin D or PTH levels or fracture prevalence with the BMI. No association was found also with any other reported fracture type. However the self-reported vertebral fracture prevalence was much lower than expected and underreporting might have occurred . Three sAdvanced age is associated with a declining renal function, another causal factor for SHPT in the elderly ,32. Its Our study has several limitations. In the first place, the number of subjects with fractures was relatively low, thus limiting the statistical power of the analysis. Second, though it is well accepted that the UV radiation in Bulgaria in late autumn and winter is low, the study could benefit from an assessment of the sun exposure of the studied subjects. Third, the fractures were self-reported, which precludes the assessment of vertebral fractures and also introduces imprecision concerning the time since the fracture. The temporal difference between the time of the fractures and the study limits the conclusiveness of the results. We had no data on falls that may be an important mediator between vitamin D and fractures. The cross-sectional design on the other hand does not permit causality inferences.In conclusion, we observed a high prevalence of vitamin D deficiency and SHPT in the studied nursing home residents. Hip fracture risk was associated with the elevated PTH and not directly to the vitamin D levels. Since vitamin D deficiency is the major cause of SHPT in the elderly, sufficient vitamin D supplementation should be recommended for the nursing home residents for whom the evidence for hip fracture reduction with supplementation is compelling .


In the course of the SARS-CoV-2 pandemic, multiple vaccines were developed. Little was known about reactogenicity and safety in comparison to established vaccines, e.g. influenza, pneumococcus, or herpes zoster. Therefore, the present study aimed to compare self-reported side effects in persons vaccinated against SARS-CoV-2 with the incidence of side effects in persons receiving one of the established vaccines.A longitudinal observational study was conducted over a total of 124 days using web-based surveys. Persons receiving either a vaccination against SARS-CoV-2 or one of the established vaccines (comparator group) were included. In the first questionnaire (short-term survey), 2 weeks after vaccination, mainly local and systemic complaints were evaluated. The long-term survey (42 days after vaccination) and follow-up survey (124 weeks after vaccination) focused on medical consultations for any reason. Multivariate analyses were conducted to determine the influence of the vaccine type (SARS-CoV-2 vs. comparator) and demographic factors.In total, data from 16,636 participants were included. Self-reported reactogenicity was lowest in the comparator group (53.2%) and highest in the ChAdOx1 group (85.3%). Local reactions were reported most frequently after mRNA-1273 (73.9%) and systemic reactions mainly after vector-based vaccines (79.8%). Almost all SARS-CoV-2 vaccines showed increased odds of reporting local or systemic reactions. Approximately equal proportions of participants reported medical consultations. None in the comparator group suspected a link to vaccination, while this was true for just over one in 10 in the mRNA-1273 group. The multivariate analysis showed that people with SARS-CoV-2 vaccination were not more likely to report medical consultations; patients who had received a regimen with at least one ChAdOx1 were even less likely to report medical consultations. Younger age, female gender and higher comorbidity were mostly associated with higher odds of medical consultations.The rate of adverse reactions after established vaccinations was roughly comparable to previous studies. Two weeks after vaccination, participants in the SARS-CoV-2 vaccination group reported more local and systemic local reactions than participants in the comparator group. In the further course, however, there were no higher odds of medical consultations in either of the two groups. Thus, altogether, we assume comparable safety.DRKS-ID DRKS00025881 and DRKS-ID DRKS00025373.The online version contains supplementary material available at 10.1186/s12916-023-03064-6. Startinytopenia  or myocaytopenia . This scytopenia , vaccinaytopenia . In 2016ytopenia . In 2020ytopenia .Corona Vakzin Konsortium (CoVaKo) project tries to elucidate the efficacy and safety of the SARS-CoV-2 vaccines under real-world conditions. The CoVaKo safety study reported here aimed to assess reactogenicity and self-reported health problems compared with other common vaccinations such as those against influenza or pneumococcus [Against this background, the mococcus , 16. Whimococcus , a compaWe conducted a longitudinal online cohort observational study to assess health problems and healthcare utilisation after vaccination against SARS-CoV-2 and multiple other vaccinations. Reporting of the study is based on the STROBE  recommendations  and influenza, pneumococcus, tick-borne encephalitis (TBE), tetanus and diphtheria (Td) vaccinations with or without pertussis and poliomyelitis (TdaP and TdaP-IPV), and herpes zoster (comparator group). Short- and long-term surveys were sent 14 and 40 days after vaccination, respectively. Additionally, participants received the follow-up survey 124 days after vaccination.Due to the changing SARS-CoV-2 vaccination recommendations over time, the intervals between first and second vaccinations changed over the course of the study. It was therefore decided to omit individual survey time points when short- and long-term surveys were in an unfavourable temporal relationship. Figure The recruitment strategy and the surveys were evaluated in a feasibility study   and had received a vaccination against SARS-CoV-2, influenza, pneumococcus, tickborne encephalitis, tetanus with or without diphtheria/pertussis/poliomyelitis, and/or herpes zoster in the last 124 days were included. Exclusion criteria were incomplete registrations, registration before vaccination date or later than 124 days after vaccination of first or single dose, and an interval between prime and boost SARS-CoV-2 immunisation of less than 14 days.At registration, participants were asked about socio-demographic characteristics, comorbidities and information about the vaccination including brand name and batch number. Morbidity was assessed based on a modified German version of the Self-Administered Comorbidity Questionnaire (m-SCQ-D) , 22. In Data collection was carried out with the web-based software platform REDCap (Research Electronic Data Capture), hosted at Universitätsklinikum Erlangen , 24. DatIn case a person registered twice with the same email address, the data records were merged. If two participants used the same email address, both data sets were handled separately. For purposes of plausibility testing, it was checked whether the invitation links were sent at the correct time with regard to the vaccination date. If the answers were sent at an incorrect time, they were counted as missing. In case of implausible data on age (year of birth before 1900), weight (less than 30 kg or more than 300 kg), height (less than 100 cm or more than 250 cm) and/or pregnancy , the corresponding variables were set to missing. Batch numbers were checked for plausibility and compared with the database of the Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte). Data records with invalid batch numbers were excluded. The total number of completed questionnaires included in the analysis was 16,636.Short-term survey: BNT162b2, mRNA-1273, ChAdOx1, Ad26.COV2.S, and comparator vaccinationsLong-term survey: BNT162b2, mRNA-1273, ChAdOx1, Ad26.COV2.S, and comparator vaccinationsFollow-up survey: homologous mRNA (BNT162b2 + BNT162b2 or mRNA-1273 + mRNA-1273), homologous vector (ChAdOx1 + ChAdOx1), heterologous immunisation (ChAdOx1 + BNT162b2 or ChAdOx1 + mRNA-1273), and comparator vaccinationsThe analysis compared the following cohorts:The data selection and preparation process are depicted in Fig. Age was determined by subtracting the reported year of birth from the registration year (2021/2022). Sociodemographic characteristics and comorbidities are reported as proportion or as mean/median. Comorbidity in form of m-SCQ-D was calculated. Consequences of reactions were queried in a multiple-choice question. The consequence that is considered to be the most severe is being reported . Health problems are reported as absolute and relative frequencies.To compare cohorts, multivariable logistic regressions were performed. For the short-term surveys, the outcome was local and systemic reactions. For the long-term and follow-up surveys, the outcomes were outpatient and inpatient medical consultations that had occurred or were planned. Predictors included vaccination type (short-term and long-term surveys) or vaccination regimen (follow-up survey), respectively, age (in years), gender, m-SCQ-D, vaccination-registration interval (in days), and another vaccination in the 8 weeks prior to registration or since answering the last survey. Reference was represented by comparator vaccinations. We conducted a subgroup analysis including only those participants who had received influenza vaccination in the reference group.R Statistical Software  was used for conducting data preparation, analyses, and figure creation.In total, 3266 short-term surveys, 3379 long-term surveys and 9991 follow-up surveys have been included in the analysis. In the short-term survey, the SARS-CoV-2 vaccination group comprised 3063 participants whereas the comparator group included 203 individuals . If one was reported, medication intake was most frequent, ranging from 2.3% in the comparator group up to 8.5% in the mRNA-1273 group. Sick leave and ambulatory consultation were less frequent consequences . Hospital outpatient consultation only occurred very rarely and only in participants with mRNA-1273. Hospitalisations due to local reactions were reported in none of the groups.Systemic reactions entailed more consequences than local reactions. While the majority of participants in the comparator cohort (81.8%) and in the mRNA cohorts (71.3%/67.1%) as well reported no consequences, this proportion was markedly lower in those vaccinated with vector-based vaccines (46.2%/40.8%). In all groups, medication intake was the most common consequence but with distinct differences, being lowest in comparator vaccines (13.6%) and highest in vector-based vaccines (33.3%/37.9%). In a similar manner, sick leave was reported more frequently in the vector-based cohorts (11.0%/23.3%) than in the mRNA (4.5%/5.4%) or comparator (3.0%) cohorts. Ambulatory consultations occurred roughly in equally low frequencies in all groups, with a minimum in comparator-vaccinated participants. Hospital outpatient consultations and hospitalisations due to systemic reactions were only reported by participants vaccinated with BNT162b2 and were very rare events.Unsolicited reactions were reported more frequently in patients with vaccinations against SARS-CoV-2 than those with comparator vaccinations (11.0% vs. 5.4%). For participants with comparator vaccinations, however, these had consequences more frequently in contrast to participants with SARS-CoV-2 vaccinations, mainly driven by taking sick leave.In contrast to the comparator group, participants in the SARS-CoV-2 vaccination group showed higher odds of reporting any, local, or systemic reactions Table . VaccinaIn the case of systemic reactions, the odds of reporting were highly increased in participants with ChAdOx1  and Ad26.COV2.S . mRNA-1273  and BNT162b2  both increased reporting significantly, but on a lower level. Younger age and female gender were as well associated with an increased reporting of systemic reactions. Lower m-SCQ-D and shorter interval between vaccination and registration were significantly associated with lower odds of reporting systemic reactions. Having another vaccination had no influence on reporting systemic reactions.The subgroup analysis, which restricted the comparator group to influenza vaccinations, showed no relevant changes in the predictors (data not shown). However, we observed that participants with Ad26.COV2.S vaccine reported local reactions significantly more often than people with influenza vaccination .In both the long-term and the follow-up survey, approximately equal parts of participants reported having sought medical consultation (14.2% vs. 13.0 to 16.7% for long-term surveys and 20.9% vs. 16.4 to 21.6% for follow-up surveys). The proportion of participants who had sought medical consultation, declared that their health problems were unknown and that they suspected a connection with the vaccination was lowest in the comparison group (2.1% vs. 3.1 to 9.4% for long-term surveys and 0.0% vs. 2.3 to 4.2% for follow-up surveys) . Female gender, higher m-SCQ-D, and longer interval between vaccination and registration was associated with more reports of outpatient consultations. Age had no influence on reporting outpatient consultations. In a similar manner, fewer inpatient consultations were reported by patients with heterologous vaccination, but not with ChAdOx1 homologous immunisation . Age and gender had no influence on reporting of inpatient consultations, while the influence of m-SCQ-D and interval to registration persisted. Receiving another vaccination in the 2 months prior to registration or since answering the last survey had no influence on reporting out- or inpatient consultations in the long-term as well as in the follow-up surveys.Restricting the reference group to only those participants who had received influenza vaccination did not lead to relevant changes in the results of the long-term and follow-up survey (data not shown). However, the results showed that participants with homologous ChAdOx1 vaccination — in line with the results for participants with heterologous vaccination in the main analysis — were significantly less likely to report inpatient consultations in the follow-up survey than people with influenza vaccination .A longitudinal observational study was conducted to contrast reactogenicity and medical consultations following SARS-CoV-2 and comparator vaccinations. In the comparator group, local and systemic reactions were less frequently reported. For both local and systemic reactions, those vaccinated with comparator vaccinations were more likely to report no consequences. If consequences were reported, medication intake and sick leave were most commonly reported in all groups. Multivariate regression analyses showed a strong influence of younger age, female gender, and more comorbidities on reporting local as well as systemic reactions. In the long-term survey and the follow-up survey, a comparable frequency of seeking medical consultation in all groups has been observed. Comparator-vaccinated patients were significantly less likely to suspect an association with the vaccination than patients who had received SARS-CoV-2 vaccination. In the follow-up survey, participants vaccinated with a regime including ChAdOx1 were less likely to report out- or inpatient medical consultations than participants in the comparator group.Published data on side effects of the comparator vaccines differ strongly and are of limited comparability, e.g. due to the different approval status of sera in different countries, but also due to different survey designs, outcomes or study populations. Low incidences of local side effects in up to half of all patients have been reported after administration of different vaccines against influenza, FSME-Immun® (TBE), and Encepur® (TBE), with reports ranging between 6.7 and 44.7% of patients –28. In aTo our knowledge, consequences in the form of medication intake, sick leave, or medical consultations had rather been included as outcomes of the vaccination in vaccine studies before SARS-CoV-2 than as side effects of the vaccinations. Very few studies discussed these consequences as reactions to the vaccination itself, such as Nichol et al. who reported a work loss due to side effects of a influenza vaccination in healthy subjects of 2 days per 100 persons . SeekingFemale gender had a significant influence on reports of outpatient medical consultations, but not of inpatient medical consultations. Gender-related differences in consultation frequency have already been described and discussed several times and contrast different health behaviours in similar symptoms on one side with different symptom compositions on the other –44. One Due to the design as a prospective observational study, group sizes differed significantly. While 3063 participants responded to the first survey with SARS-CoV-2 vaccination, this number increased to a total of 9613 participants in the follow-up survey. For the comparator vaccinations, by contrast, responses were only by 203 (short-term survey), 337 (long-term survey) and 378 participants (follow-up survey), respectively. This pronounced difference makes comparisons of adverse events with a very low incidence particularly difficult, even more so because the survey was powered for an event rate of 0.1%. Therefore, we performed a multivariate logistic regression to consider the different vaccination recommendations with regard to gender and age, as descriptive results may not be transferable to the German population as a whole. Secondly, resulting from the limited number of participants who had received one of the comparator vaccinations, we opted to combine the corresponding group. Consequently, this group comprised above all, though not exclusively, adjuvanted inactivated vaccines for which greater reactogenicity has been reported . Thus, wParticipants in our survey tended to be younger than would be expected based on vaccination recommendations, presumably due to an age-related digital divide in the sense of a selection bias. As higher reactogenicity after vaccination against SARS-CoV-2 in younger patients has been reported before , we assuOne of the strengths of the survey is the reporting of adverse events by the participants themselves, i.e. patient-reported outcome measures. As the data basis does not consist of medical reports but of self-reports, this survey allows for a direct and unmediated comparison of the frequency of reactions and medical consultations. However, due to this direct reporting by patients, it must be considered that non-response bias might lead to a skewing of the results and are therefore subject to uncertainty.Participants in the SARS-CoV-2 vaccination group were more likely to report local and systemic side effects 14 days after their vaccination than those in the comparator group. However, 16 weeks later, there was no higher reporting of seeking medical consultations in the SARS-CoV-2 vaccination group. Patients who had received ChAdOx1 at least once even reported significantly fewer outpatient and inpatient consultations than the comparator group. Adverse events and medical consultations were reported significantly more frequently by women, younger people and people with pre-existing medical conditions.Additional file 1. STROBE.Additional file 2. Surveys.


The mortality rate of patients diagnosed with sepsis is high. To date, many markers in sepsis patients have been studied to diagnose, determine their prognosis, and contribute to treatment. These studies were conducted in both experimental and clinical settings, but clinical trials remain limited. Therefore, more well-planned clinical studies are needed in patients with sepsis.The current study aimed to examine the prognostic role of signal peptide-CUB-epidermal growth factor-like domain-containing protein 1 (SCUBE-1) in sepsis and sepsis-related mortality. We also wanted to study its relationship with inflammatory markers and scoring systems.This prospective, cross-sectional, observational study included a total of 187 sepsis cases treated in the intensive care unit. Venous samples were obtained after diagnosis. The patients were separated into 2 groups: (1) the survivor group who were discharged or transferred within 28 days of the first diagnosis and (2) the nonsurvivor group who died within 28 days of the first diagnosis.The SCUBE-1, C-reactive protein, procalcitonin, creatinine, lactate values, acute physiology and chronic health evaluation 2, sequential organ failure assessment scores were significantly higher in the survivor group, and platelets were higher in the survivor group. In addition, SCUBE-1 positively correlated with the inflammatory markers C-reactive protein, lactate, sequential organ failure assessment, and acute physiology and chronic health evaluation 2. Additionally, the SCUBE-1 value predicts 28-day mortality, and the optimal cutoff value for predicting mortality is 4,73 pg/mL.Sepsis is a disease with high mortality. SCUBE-1 can be used as a new prognostic factor for sepsis patients. It is one of the leading causes of death among patients in noncoronary intensive care units (ICUs).Sepsis is a clinical syndrome that involves physiological, biological, and biochemical abnormalities caused by a dysregulated inflammatory response to infection. Sepsis and the inflammatory response that can lead to multiple organ dysfunction syndrome and death. It is known that the most common symptoms of severe organ dysfunction are acute respiratory distress syndrome, acute kidney failure, and extensive intravascular coagulation. Scoring systems are used to predict disease severity and mortality in intensive care patients, including patients with sepsis. These scoring systems are also useful for standardizing research and comparing patient care quality in ICUs. Furthermore, they are widely used worldwide. The Acute Physiology and Chronic Health Evaluation 2 (APACHE-2) scoring system is the most used scoring system in the World. APACHE-2. It consists of three parts: acute physiology score, age, and chronic health assessment. In this way, the acute and chronic health status of the patient is evaluated. The sequential organ failure assessment (SOFA) scoring system is used to diagnose sepsis patients in the ICU and determine their prognosis. SOFA uses simple measurements of major organ dysfunction to calculate a severity score, and it does not contain any parameters related to the patient's chronic health status.The severity of the disease seems to be increasing. The SCUBE family has three different members. SCUBE-1 and 2 are cell-surface proteins that are expressed from platelets and endothelial cells. In particular, SCUBE-1 is highly expressed in platelets. SCUBE-1 increases platelet aggregation and adhesion. It has been identified as a potential thrombosis marker. SCUBE 3 is expressed during embryogenesis.Signal peptide-CUB-Epidermal growth factor-like domain-containing protein 1 (SCUBE-1) is a cell surface glycoprotein that is present in platelet and endothelial cells.Sepsis is a condition caused by severe inflammation that leads to microcirculation disorder, platelet activation, and endothelial damage. SCUBE-1 is a cell-surface protein that is expressed from platelets and endothelial cells so that we hypotyzed SCUBE-1 may have a role in the sepsis pathway.Laboratory findings, especially inflammatory markers such as C-reactive protein (CRP) and procalcitonin (PCT), help in diagnosing and monitoring sepsis prognosis.To date, many markers in sepsis patients have been studied to diagnose, determine their prognosis, and contribute to treatment. These studies were conducted in both experimental and clinical settings. However, although the majority of these studies’ preclinical results were positive, their benefits in clinical trials remained limited.The primary purpose of this study was to investigate the prognostic role of SCUBE-1 in sepsis and sepsis-related mortality. Our other goals are to examine the relationship between SCUBE-1 with scoring systems and inflammatory markers.1.1Sepsis is a clinical syndrome caused by a dysregulated inflammatory response to infection. Sepsis and inflammatory response can lead to multiple organ dysfunction syndrome and death.Scoring systems and inflammatory markers are used to predict disease severity and mortality in sepsis.SCUBE1 is a cell surface glycoprotein that is present in platelet and endothelial cells; it also has a relationship with thrombus and endothelial dysfunction.The current study demonstrated that SCUBE-1 is an independent mortality predictor in sepsis patients; it also has a positive correlation with inflammatory biomarkers and APACHE II.22.1 All patients aged >18 years who met the criteria were included in the study. Patients were excluded from the study if they had cancer, were pregnant, had used antibiotics in the 2 weeks before presentation at the hospital, or needed vasopressors at the time of admission. The patients were separated into 2 groups:This prospective, cross-sectional study included a total of 187 sepsis cases treated in the tertiary medical ICU of Adana City Training and Research Hospital between July 2019 and November 2019. Hospital is regional hospital and has thirty tertiary medical ICU bed. Sepsis was diagnosed according to the Sepsis-3 criteria.1.the survivor group who were discharged or transferred within 28 days of the first diagnosis and2.the nonsurvivor group who died within 28 days of the first diagnosis.A flow diagram for this study is presented in Figure Approval for the study was granted by the Local Ethics Committee of Çukurova University Medicine Faculty . Informed consent was obtained from all patients or their legal guardians.2.2A 5 ml venous blood sample was taken from all patients after diagnosis before treatment. These venous blood samples were centrifuged at 4000 rpm for 10 min, and the serum samples obtained were frozen and stored at –80°C until assay. Biochemical analyses were performed using an autoanalyzer. SCUBE-1 levels were determined using a commercial enzyme-linked immunosorbent analysis (ELISA) kit .2.3t test or the Mann-Whitney U test according to the conformity of the data to normal distribution. The groups were compared with respect to categorical variables using the Chi-square test or Fisher exact test. Correlation coefficients of numerical variables that did not conform to at least 1 normal distribution measurement were calculated with the Pearson test and statistical significance with the Spearman test. Receiver operating characteristic (ROC) curve analysis was used to determine the sensitivity and specificity of the predictive value of SCUBE-1 for clinical outcomes. The optimal cutoff value of SCUBE-1 was derived from the Youden index. Kaplan-Meier curves were constructed using SCUBE-1 groups as strata and compared using the log-rank test. To identify risk factors for 28-day mortality, a multiple Cox proportional hazards regression model was performed.Statistical analysis was performed using SPSS version 22 software . Continuous variables were expressed as mean ± standard deviation, median (interquartile range), and categorical variables as number (n) and percentage (%). The patients were separated into 2 groups: survivors and nonsurvivors. Comparisons of continuous variables between the groups were made using the Student 3P = .641). When the groups were analyzed in terms of age, the nonsurvivor group consisted of older individuals (P = .007). According to the clinical parameters, the median APACHE-2 (P < .001) and SOFA score (P < .001) were higher in the nonsurvivor group, and no difference was determined with respect to the Charlson comorbidity index (P = .145). The demographics and clinical characteristics of all study patients are shown in Table The study included 187 patients, with a median age of 74 years (interquartile range 66–80). One hundred eighty-seven of the patients, 43.2% were male. The survivors group included 123 patients and 64 nonsurvivors. The mortality rate was determined to be 35.1%. The groups had similar characteristics in terms of gender distribution (P = .034), lactate (P = .005), CRP (P = .016), PCT (P = .036), and SCUBE-1 (P < .001) were significantly higher in the nonsurvivor group. The mean platelet count (P = .036) was higher in the survivor group. The median of the other parameters was similar in both groups. The laboratory characteristics of all study patients are shown in Table P < .001), SOFA , lactate , and CRP  , SOFA , CRP , and SCUBE-1  were 4 independent prognostic factors for 28-day mortality in septic patients.To investigate potential prognostic factors for 28-day mortality in septic patients, univariate and multivariate Cox proportional hazards regression analyses were performed using the potential risk factors Table . The uniP < .001; CI: 0.747–0.879), a cutoff value of ≥4,73, a sensitivity of 81.3%, and a specificity of 75.6%, respectively.As shown in Figure P-value, sensitivity, and specificity. ROC curve analysis showed that APACHE II  cut-off value of ≥24.5 a sensitivity of 79.7%, and a specificity of 84.6%, SCUBE-1  a cut-off value of ≥4.73 a sensitivity of 81.3%, and a specificity of 75.6%, SOFA  cut-off value of ≥6.50 a sensitivity of 64.1%, and a specificity of 74.6%, CRP  cut of value of ≥29.6 a sensitivity of 59.4%, and a specificity of 57.7%, could predict increased risk of 28-day mortality in sepsis patients  for risk of 28-day mortality were included in a ROC curve analysis. In terms of cut of value, AUC, P < .001).According to the cutoff value, patients were categorized into high SCUBE-1 levels ≥4,73) and low SCUBE-1 levels . Figure  and low 4Various biochemical markers have been explored to determine the prognosis of septic patients, but different results have been obtained. To our knowledge, this is the first study to examine the relationship between SCUBE-1 and the prognosis of septic patients. The results of this study demonstrated that SCUBE-1 is an independent prognostic factor in septic patients. In addition, SCUBE-1 showed a positive correlation with accepted inflammatory biomarkers and APACHE-2. Microcirculatory injuries may result from imbalances in the coagulation and fibrinolytic systems, both of which are activated during sepsis. The increase in receptor-mediated neutrophil-endothelial cell adherence induces the secretion of reactive oxygen species, lytic enzymes, and vasoactive substances  into the extracellular area. This is the beginning of the pathway that damages endothelial cells. Microcirculation injury and endothelial lesions reduce the cross-sectional area available for tissue oxygen exchange, disrupt tissue oxygenation, and cause tissue ischemia and cellular injury.Many proinflammatory cytokines are released in septic patients, which causes the progression of a local infection to sepsis. Tumor necrosis factor-alpha and interleukin-1 are the primary levels, with plasma levels peaking early and eventually falling to undetectable levels. Cytokines can cause fever, hypotension, leukocytosis, and the simultaneous activation of coagulation and fibrinolysis. It has been previously reported that SCUBE-1 could have a role in cardiovascular, metabolic, and immunological diseases.,13,14 Based on the increase of SCUBE-1 with platelet activation, Türkmen et al demonstrated plasma SCUBE-1 level as a potential marker for diagnosing the early stage of acute mesenteric ischemia. Also, Dai et al demonstrated that plasma SCUBE-1 level was significantly elevated in acute coronary syndrome and acute ischemic stroke. Bayoglu et al demonstrated that SCUBE1 could be a potential marker for the early detection of fetoplacental endothelial dysfunction and related maternal and fetal complications. Previous studies have demonstrated the relationship between SCUBE-1 and thrombus, endothelial dysfunction. Since sepsis is a condition caused by severe inflammation that leads to microcirculation disorder, platelet activation, and endothelial damage, we examined the relationship between SCUBE-1 and sepsis disease in our study.SCUBE1 is a cell surface glycoprotein that is present in platelet and endothelial cells.Our study's outcomes supported our hypothesis; the SCUBE-1 level was found to be higher in non-surviving patients than in survivors. According to our study, the high plasma level of SCUBE-1 indicates that the disease will progress severely. SCUBE-1 has prognostic importance in patients with sepsis. SCUBE-1 values exceeding ≥4.73 pg/mL predict 28-day mortality.We also studied biochemical and inflammatory markers; CRP, PCT, creatinine, and lactate levels were significantly higher in the nonsurvivor group; platelets were higher significantly in the survivor group. In addition to these results, it has been demonstrated that the level of SCUBE-1 positively correlates with the inflammatory marker CRP and impaired tissue oxygenation marker lactate.,17 Predictive scoring systems are used to predict mortality in ICU patients. The APACHE II and SOFA scoring systems have been widely validated and used by many ICUs to classify sepsis severity and predict hospital mortality.,6 In our study, APACHE-2 and SOFA scores were found to be statistically significant in patients who died. This is eventually compatible with the literature. In many studies in the literature, the prognostic value of biomarkers screened for sepsis has been compared with scoring systems. In our study, we compared SCUBE-1 with scoring systems and showed a positive correlation between APACHE-2 and SOFA.,19,20Sepsis is associated with high mortality and substantial morbidity. Like in our study, in multicenter studies, up to 35% to 40% of patients with sepsis die from the condition.Our study's strengths are that SCUBE-1 predicts 28-day mortality and is correlated with other mortality predictors APACHE-2 and SOFA. It is also correlated with the proinflammatory marker CRP and impaired tissue oxygenation marker lactate.This study has some limitations that should be discussed. The most important limitations of our study are the fact that it is a single-center study. We performed SCUBE-1 measurements from patients only after sepsis diagnosis. Making 1 measurement in this design is another limitation. In addition, there were not enough patients in some subgroups for the source of sepsis. For this reason, statistical analysis of the sepsis source was not performed. This is another limitation of our study. Finally, SCUBE-1 is a new biomarker, so it may not be possible to control all of the variables affecting SCUBE-1 levels.5In conclusion, SCUBE-1 levels have the potential to be used as a mortality predictor in septic patients. Serum SCUBE-1 levels are correlated with inflammatory markers, lactate, APACHE-2, SOFA, and disease severity. Nevertheless, there is a need for further studies to examine the specific role of SCUBE-1 in sepsis and sepsis-related mortality. In addition, the rate of change of SCUBE-1 levels after sepsis treatment should be examined.Conceptualization: Hüseyin Avni Findikli.Data curation: Murat Erdogan, İrem Okuducu Teran.Formal analysis: İrem Okuducu Teran.Investigation: Murat Erdogan.Methodology: Hüseyin Avni Findikli.Project administration: Murat Erdogan.Resources: İrem Okuducu Teran.Writing – original draft: Murat Erdogan.Writing – review & editing: Murat Erdogan.